Heinrich
Gottlinger, MD, PhD
Discoveries in Luban, Gottlinger labs point to new
strategies for disabling viruses
(September 30, 2015) A
pair of studies in the journal Nature, one by Jeremy Luban, MD, and colleagues
in Italy and Switzerland, and the other by Heinrich Gottlinger, MD, PhD, and
colleagues; have identified genes that disable HIV-1, suggesting a promising
new strategy for battling the virus that causes AIDS.
The studies, published online Sept. 30, show that the host
cell membrane proteins SERINC5 and SERINC3 greatly reduce the virulence of
HIV-1 by blocking the ability of the virus to infect new cells. HIV-1 encodes a
protein called Nef that counteracts the SERINCs. New drugs that target the
HIV-1 protein Nef would permit the SERINC proteins to inactivate the virus. The
papers will appear in the Oct. 8 Nature print edition.
“It’s amazing, the magnitude of the effect that these
proteins have on infectivity,” said Dr. Luban, the David J. Freelander
Professor in AIDS Research and professor of molecular medicine. “The SERINC
proteins reduce the infectivity of HIV-1 virions by more than 100-fold.”
Jeremy Luban, MD
Dr. Gottlinger, professor of molecular, cell & cancer
biology and principal investigator of one of the studies, said, “The ability of
HIV to inhibit these SERINC proteins has a profound impact on its capacity to
infect other cells. Disrupting this mechanism could be a very powerful strategy
for treating HIV and similar viruses that express the Nef protein.”
The studies, each done independently, used different, yet
complementary, methodologies to unravel the complex interaction between the
HIV-1 protein Nef and the cell surface membrane proteins SERINC5 and SERINC3,
both of which are expressed in the immune system’s T cells. Luban, working with
former members of his lab Massimo Pizzato, PhD, now of the University of Trento
in Italy, and Federico Santoni of the University of Geneva in Switzerland,
performed massively parallel sequencing on 31 human cell lines that differed in
terms of the magnitude of dependence on Nef for HIV-1 replication.
Independently, Gottlinger approached the problem biochemically. Conducting
proteomic analysis of purified virions, he was able to identify host cell
proteins that Nef regulated.